The benefit of post-mastectomy radiotherapy (PMRT) for pT1-2N1M0 breast cancer patients currently remains controversial. This study was conducted to investigate whether pT1-2N1M0 breast cancer patients could benefit from PMRT based on RecurIndex assay. The clinical data of 213 pT1-2N1M0 breast cancer patients were retrospectively analyzed. Through RecurIndex assay, 81 cases were assessed as the low risk, and 132 as the high risk. Compared with low-risk patients, high-risk patients especially those not receiving PMRT had a significantly increased risk of recurrence and metastasis, and worse 7-year local-regional recurrence-free interval (LRFI), distance recurrence-free interval (DRFI) and recurrence-free survival (RFS) rates. PMRT-based subgroup analysis indicated no significant differences between the low-risk patients with and without PMRT in 7-year LRFI, DRFI, RFS and overall survival (OS) rates, but apparent differences were all shown between the high-risk patients with and without PMRT in 7-year LRFI, DRFI, RFS and OS rates. Overall, for pT1-2N1M0 breast cancer patients at low risk of recurrence and metastasis stratified by RecurIndex assay, there may be a phenomenon of no PMRT benefits, while for those at high risk, use of PMRT may produce survival benefits. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.